Auditory research into the neural basis of communication sound processing has generally been conducted without accounting for the social contexts in which communication naturally occurs. Hence, how the auditory system is able detect, discriminate and categorize communication calls despite natural speaker variability is poorly understood, as are the mechanisms by which social interactions affect this processing. Our long-term goal is to uncover the circuit, cellular and molecular mechanisms underlying the auditory system's encoding of socially-acquired vocalizations, so that causes underlying deficits in natural communication processing can be inferred. We pursue this in a mouse model of ultrasound communication wherein two categories of calls (those emitted by mouse pups and by adult males) carry different meanings and can have different levels of behavioral relevance to a female. The objective here is to uncover how the representation of these call categories is transformed by hierarchical processing from a primary to a higher-order auditory cortical field, and how different natural social experiences with the calls produce coding changes. Our central hypothesis is that the transformation refines call coding to facilitate communication tasks, and that social experience and neurochemical systems modify this neural transformation as behavioral relevance is acquired. The rationale for this research is that once we know the manner by which neural plasticity in auditory cortex shapes the coding of behaviorally relevant calls, we will be able to exploit the transgenic advantages of the mouse model to dissect the detailed mechanisms enabling these changes. Using extracellular electrophysiology in awake mice, we will test our hypothesis with three specific aims. First, we will determine how the neural transformation normally functions to refine the encoding of behaviorally relevant calls by recording from animals that recognize the significance of pup calls (mothers). Second, we will determine how social experience with pups modifies this neural transformation by recording from virgin females that help care for pups (co-carers). Third, we will determine how a key social neurochemical implicated in pup call recognition, estrogen, works with pup care experience to modify the neural transformation by recording from hormonally manipulated co-carers. This proposal's significance lies in its unique ability to bridge the scientific gap between sensory and social/behavioral neuroscience in an animal model in which we can pursue future studies of a high level auditory function (communication) from a system down to a molecular level. PUBLIC HEALTH RELEVANCE: This research will enable us to discover mechanisms underlying the natural functioning of the processing stream between a primary and higher-order auditory cortical field in the context of species-specific communication. By elucidating the normal operation of this system, our results will be important in implicating aspects of communication coding and plasticity that may fail in auditory processing disorders, social disorders with auditory dysfunctions, hearing loss and temporal lobe strokes.